Nu-(diphenylmethylbenzoyl) amino-alkanoic acids



3,086,979 N-(DIPHENYLMETHYLBENZOYL)AMINO- ALKANOIC'ACIDS Carl Peter Krimmel, Mundelein, IlL, assignor to G. D. Searle & Co., Chicago, Ill., a corporation of Delaware No Drawing. Filed Juiy 19, 1960, Ser. No. 43,726 9 Claims. (Cl. 260-389) The present invention relates to compounds of the formula with an amino acid. Embodiments containing more than one amide group are also prepared by condensation "of an acid of the formula with the ester of an amino acid in the presence of dir, 3,086,979 Patented. Apr. 23, 1963 ice a solution of 22 parts of p-diphenylmethylbenzoyl chloride in 395 parts of acetone; a slight rise in temperature occurs. The resultant mixture is heated in an open vessel until the acetone is evaporated, and the aqueous solution thus obtained is acidified with dilute hydrochloric acid. The resultant gum is treated with ice cold water until it becomes friable; and the granules are dried in air. The crude N-(p-diphenylmethyl'benzoyl)glycine thus obtained is crystallized from isopropylalcohol with charcoal decolorization; the puirfied product melts at 210-218. The structure may be expressed as Example 2 N (.p diphenylmethylbenzoyl)-/3-alanine.-Sub'stitution of '11 parts of fi-alanine for the glycine of Example'l gives, by the procedure therein detailed, N-(p-diphenylmethylbenzoyl)-,B-alanine. The crude sample thus obv tained is recrystallized from benzene --with charcoal decyclohexylcarbodiimide followed by conversion to the i free acid.

The following. examples describe; in detailcompounds illustrative of the present invention and methods for their manufacture; the invention is not to be construed as limited thereby either. in spirit or in scope. Iri-the examples to follow. temperatures are given in degrees centigrade, and amounts of materials in parts by weight.

Example 1 N-(p-diphenylmethylbenzoyl)glycine.A mixture of 20 parts of p-diphenylmethylbenzoic acid, 33 parts of thionyl chloride and 128 parts of carbon tetrachloride is heated under reflux for 3 hours. At the end of this time the solvent and excess thionyl chloride are distilled on the steam bath at diminished pressure; the last traces of thionyl chloride are removed by addition of anhydrous benzene, and distillation. The resultant p-diphenylmethylbenzoylchlorideis used without further purification. To a stirred solution of 9 parts of glycine and 14 parts of sodium hydroxide in 350 parts of water is added col-orization; the pure sample melts at 157159. The

structure may be expressed as Example 3 N-(p diphenylmethylbenzoyl)-'y-amin0butyric acid.- Substitution of 12 parts of 'y-aminobutyric acid for-the glycine of Example l.gives, by the procedure therein detailed, crude N-(p-diphenylmethylbenzoyl)-'y-aminobutyric acid; the pure sample, prepared by recrystallization from benzene with charcoal decolorization, melts at -169". The structure mayibe expressed as i -onnornomcmooon Example 4 'N (p-diphenylmethylbenzoyl)alanine.4ubstitution of 11 parts of alanine'for the glycine of Example 1 gives by the procedure therein detailed,'N-(p-diphenylmethylbenzoyl)alanine. The structure may be expressed as Q r Q-hnrrdnooon Example'5 N-(m-diphenylmethylbenzoyl)glycine.Substitution of 22 parts of 'm diphenylmethylbenzoyl chloride for the p-diphenylmethylbenzoyl chloridebf Example 1 gives, by

the procedure therein detailed, N-(m-diphenylmethylbenzoyl)-glycine. The structure may be expressed as ii ONHCHaO O OH Example 6 N-(m diphenylmethylbenzoyl)-[3-alanine.&1bstitution of 22 parts of m-diphenylmethylbenzoyl chloride for the p-diphenylmethylbenzoyl chloride and 11 parts of B- alanine for the glycine of Example 1 gives, by the procedure therein detailed, crude N-(m-diphenylmethylbenzoyl)-;8-alanine. The white gum which separates on acidification shows no tendency to solidify. The supernatant liquid is removed by decantation, and the gum is washed with fresh water. The residue is taken up in 616 parts of benzene, and final traces of water are removed by azeotropic distillation. The benzene solution is subjected to charcoal decolorization, and cooled to give the pure compound, melting at 156-158. The structure may be expressed as Example 7 N-(m-diphenylmethylbenzoyl)-a-aminobutyric acid.-- Substitution of 22 parts of m-diphenylmethylbenzoyl chloride for the p-diphenylmethylbenzoyl chloride and 12 parts of waminobutyric acid for the glycine of Example 1 gives, by the procedure therein detailed, N-(m-diphenyl methylbenzoyl)-a-aminobutyric acid. The structure may be expressed as o onion, @dmabnooorr Example 8 l @imnomomooou Example 9 N-(o diphenylmethylbenzoyl)-y-amin0butyric acid.- Substitution of 22 parts of o-diphenylmethylbenzoyl chloride for the p-diphenylmethylbenzoyl chloride and 12 parts of 'y-aminobutyric acid for the glycine of Example 1 gives, by the procedure therein detailed, N-(o-diphenylmethylbenzoyl)-'y-aminobutyric acid. The structure may be expressed as @iimaomomomooon Example 10 N-(o-diphenylmethylbenzoyl)alanine.Substitution of 22 parts of o-diphenylmethylbenzoyl chloride for the p-diphenylmethylbenzoyl chloride and 11 parts of alanine for the glycine of Example 1 gives, by the procedure therein detailed, N-(o-diphenylmethylbenzoyl)-alanine. 25 The structure may be expressed as wherein Alk is a lower alkylene of less than 4 carbon atoms.

2. A compound of the formula 0 ll Q-JIH QONH- ower a1kylene)-C 0 OH wherein the lower alkylene radical contains less than 4 carbon atoms.

3. N-(p-diphenylmethylbenzoyl)glycine.

4. N-(p-diphenylmethylbenzoyl) -p-alanine. 5. N-(p-diphenylmethylbenzoyl)w-aminobutyric acid. 6. A compound of the formula NH- (lower alkylene) -0 O OH wherein the lower alkylene radical contains less than 4 carbon atoms.

7. N-(m-diphenylmethylbenzoyl)-[5-alanine.

8. A compound of the formula II O 6 wherein the lower alkylene radical contains less than 4 carbon atoms.

9. N-(o-diphenylmethylbenzoyl)-B-a1anine.

5 References Cited in the file of this patent UNITED STATES PATENTS 2,678,321 Krimmel May 11, 1954 

1. A COMPOUND OF THE STRUCTURAL FORMULA 